TNF and rheumatoid arthritis: Further studies performed on Roflumilast, which had just come onto the market for COPD [139], and also on Apremilast [58], which would not be approved for psoriatic arthritis until some years later, highlighted the potential of these compounds for RA demonstrating a direct correlation between PDE4 inhibition and synovial TNF-α and inflammatory cytokine and chemokine release in human synovial cells.